- Email: [email protected]
PO-0717: Radiotherapy of anal cancer: Is IMRT and VMAT a step forward?
ESTRO 33, 2014 4
UMC Utrecht, Oncologic Surgery, Utrecht, The Netherlands Julius Center, Clinical Epidemiology, Utrecht, The Netherlands
5
Purpose/Objective: Randomized controlled trials (RCTs) often experience difficulties in recruitment, external validity, follow-up, and comparability. These shortcomings become progressively important when the clinic can hardly keep up with newly available innovative treatments. We introduced the ‘cohort multiple Randomized Controlled Trial’ (cmRCT) (1), which was designed to efficiently and simultaneously evaluate new interventions, in our center. Materials and Methods: The basis of our cmRCT-design consists of a prospective observational cohort (‘ProspectIve data CollectioN Initiative on Colorectal cancer’ (PICNIC) project) in which patients optionally give separate informed consents for collection of their 1) clinical, 2) patientreported, and 3) biobank data (tumor tissue and blood samples) for (comparative) research. In a separate informed consent, they are asked to consent to 4) being randomly offered experimental interventions in the future. In practice: Rectal cancer patients that meet inclusion criteria for the experimental radiation Boost intervention are identified from all who have previously consented to experimental treatment offers. From this sub-cohort randomly selected patients are offered this Boost, which they may than accept or refuse (if standard treatment is preferred). All other patients that were not randomly selected will receive standard treatment, serving as the control-group, and will not be notified about the experimental intervention. Nevertheless, they are aware of, and have already given informed consent for their clinical and self reported data to be used for comparative research. Data is analyzed by ‘intentionto-treat’ principle, and additionally by ‘per-protocol’ or ‘complier average causal effect’ methods. Results: In the past 9 months 91 of 117 (78%) rectal cancer patients at the Radiotherapy department consented to participation in the PICNIC project (cohort). A subset of 97 patients (88%) has given separate informed consent to offer them experimental treatments. Of all eligible ‘boost-study’ subjects ..%* accepted and underwent the offered boost treatment. *nt: Patient recruitment is ongoing and updated number will be presented Conclusions: Cohort participation rate is higher than observed in conventional RCTs. A greater proportion of patients accepts ‘cohortbased random selection’ compared to ‘conventional randomization’. Efficient recruitment may contribute to improved statistical power and reduced trial-duration. This is of major interest in a time when new treatment modalities and innovations demand efficient (and rapid)evaluation. 1. Relton C. et al. Rethinking pragmatic randomised controlled trials: introducing the 'cohort multiple randomised controlled trial' design., BMJ. 2010;340:c1066. PO-0715 Post-neoadjuvant presacral radiological abnormalities in rectal cancer: Long-term risk factors analysis M. Muñoz1, F.A. Calvo1, J. Serrano1, C. Calles1, J. Laureiro1, L. Martín1, M. Gómez-Espí1, E. Del Valle2 1 Hospital Gregorio Marañón, Oncología Radioterápica, Madrid, Spain 2 Hospital Gregorio Marañón, Cirugía General, Madrid, Spain Purpose/Objective: Radiological abnormalities in the presacral area (RAPA) after neoadjuvant treatment for locally advanced rectal cancer (LARC) are complex to interpret in terms of clinical and pronostic implications. Long-term radiological changes in the posterior hemipelvis are analyzed in the context of potential risk factors for development. Computerized tomography (CT) observations are categorized to discriminate malignant versus non-malignant changes. Materials and Methods: From 04/95 to 12/10, 397 patients with LARC [≥ cT3 (93%) and/or cN + (69%)] were treated with preoperative external pelvic irradiation (81% ≥ 4500cGy) concurrent to fluoropirimidine based chemotherapy,radical surgery (sphincter preserving 68%) and presacral electron irradiation boost (IeORT) (83%). Elective adjuvant chemotherapy was considered. IeORT common characteristic were: single dose 12.5Gy (27%), electron energies 12MeV (33%), applicator diameter 5/6 cm (65%), beveled end 45º (96%). Results: With a median follow-up of 63 months, RAPA was documented in 48% of patients. Evolutive clinical and radiological subtypes were classified as presacral recurrence (4%), non-malignant mass (23%) or fibrotic linear scarring (20%). Overall survival at 5 and 10 years were 8%/0%,68%/46% and 86%/77%, respectively. Features related to the development of RAPA were: abdominoperineal resection and anterior
S27 ultralow resection (p 0,010); postoperative complications involving infection, wound dehiscence and bleeding episodes (p=0,00); operation room time (p 0,00); and ypN+ specimens (p 0,016). Non-presacral intrapelvic recurrences included 12 anastomotic (3%), 2 vaginal (0.5%), 1 urethral (0.3%) and 3 lateral pelvic sided nodes (0.8%). Conclusions: The development of post-neoadjuvant RAPA is a frequent and heterogeneous follow-up event. Risk factors identified are associated to pelvic surgical stress features and radioresistant cancer. The evolutive trend appears to be related to imaging patterns and oncological nature. In clinical practice post-neoadjuvant RAPA is rarely rectal cancer recurrence (4%). PO-0716 Image guided SBRT for treatment of liver malignancies: review of single institution 4-year experience O. Utehina1, I. Nemiro2, G. Boka1, D. Purina1, S. Maksimova1, J. Frolova1, S. Popov1, V. Boka3 1 Riga East University Hospital, Clinic of Therapeutic Radiology and Medical Physics, Riga, Latvia 2 University of Latvia, Faculty of Medicine, Riga, Latvia 3 Riga East University Hospital, Clinic of Surgery, Riga, Latvia Purpose/Objective: The purpose of this study was to evaluate intermediate term results of liver Stereotactic Body Radiotherapy (SBRT) from point of view of clinical safety and clinical effectiveness. Materials and Methods: 40 patients with 54 malignant lesions in liver treated with SBRT between 2009 and 2013 were included in analysis: 10 patients had primary liver tumors (6-hepatocellular carcinoma, 4 Klatskin tumor) and 30 had metastasis (18 from colorectal cancer and 12 from other tumor sites). Free breathing Four-dimensional Computed Tomography (4DCT) based planning was performed for all patients. No external fixation devices were used except a vacuum bag. Gross Tumor Volume (GTV), Clinical Target Volume (CTV), and Internal Target Volume (ITV) were contoured on the basis of MRI images co-registered with Maximum Intensity Projection (MIP) CT. Dose delivery was performed in consecutive days using Image Guided Volumetric Modulated Arc Therapy (IGVMAT). Prescribed dose per fraction varied from 7 to 18 Gy. Minimum PTV dose was in the range of 30 – 48 Gy. Follow-up MRI imaging was performed for all patients. This allowed to access status of tumor after treatment as well as to evaluate precision of dose delivery by imaging of typical parenchymal tissue changes arising in high dose volume after SBRT. Influence of various treatment and tumor parameters on overall survival and local relapse free survival was studied. Results: Follow-up time was in range of 5 to 49 months with median follow-up time of 13 months. Initial follow-up IMR imaging has shown that in all cases initial lesions were confined within volume of parenchymal changes. No one of the patients had any acute or late adverse effects after treatment. For four patients re-treatment by SBRT was performed due to local or other recurrence inside liver. Median overall survival was 29 months. 24-month overall survival was 53%. Distant relapse outside of the liver and initial number of liver lesions affected overall survival. Median overall survival for patients with distant relapse and without was 17 months and 36 months, respectively (p = 0.045). For patients with multiple lesions median overall survival was 13 months comparing to 29 months for patients with solitary tumor (p = 0.041). Median local recurrence free survival was 19 months. 24month local recurrence free survival was 49%. Frequency of local recurrence was affected by level of prescribed dose. 24-month local recurrence free survival was 40% for patients, which received doses ≤36 Gy and 59% for patients, which received doses above 36 Gy (p= 0.015). Conclusions: According to the intermediate term clinical experience analyzed in this study, SBRT for liver cancer is effective and safe. IGVMAT SBRT is easy to use, provides a high targeting precision, is well tolerated by patients and can be applied for retreatment. Data analysis shows that further dose escalation is needed for the better local tumor control. This possibility has to be evaluated by further studies of dose – effect relationships. Nevertheless, the study results are very promising and clearly demonstrate superiority of SBRT in treatment of liver tumors. PO-0717 Radiotherapy of anal cancer: Is IMRT and VMAT a step forward? G. Gruber1, C. Track1, C. Venhoda1, J. Hammer1, B. SpindelbalkerRenner1, E. Putz2, K.J. Spiegl1, H. Geinitz1 1 Krankenhaus Barmherzige Schwestern, Radiation Oncology, Linz, Austria 2 Krankenhaus Barmherzige Schwestern, Radiation Oncology Physics Section, Linz, Austria
S28 Purpose/Objective: In the treatment of anal cancer, intensitymodulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT, RapidArc©) were implemented at our department in 2006 and 2010, respectively. For three years we apply these techniques now to all our patients with anal cancer of all stages. To report the effect of these implementations on efficacy and toxicity we analysed all patients with anal cancer treated at our institution during the last decade. Materials and Methods: Patients who reached a complete remission 6 months after treatment were included in the evaluation (n=89, female: 65, male: 24). Fifty seven were treated with conventional techniques (mostly 3D-conformal), 9 with IMRT and 23 with VMAT. For conventional techniques the median dose was 56 Gy to the primary tumour (PT), 50 Gy to the pelvic nodes (PN) and 40 Gy to the inguinal nodes (IN). For IMRT/VMAT the respective figures were 60 Gy (PT), 50 Gy (PN) and 36 Gy (IN). Concurrent chemotherapy (5-FU with or without Mitomycin C) was administered to 83% (79% conventional and 91% IMRT/VMAT). Follow-up examinations, including MRI of the pelvis, were performed at regular intervals. A questionnaire regarding late radiation morbidity on pelvic organs as well as symptom-bother was answered by 45 patients after a median follow-up of 4 years. Results: For the whole cohort, the overall survival at 5 years was 85% and the disease specific survival 92% without differences according to treatment technique. The rates for local control, loco-regional control and disease-free survival were 88%, 82% and 75% with a trend to better rates in the IMRT/VMAT group. Mild to moderate late symptoms regarding defecation and micturition were reported by 63% and 67% of the patients, respectively. Anal incontinence was graded according to the Jorge-Wexner-Score (0 perfect continence; 20 - complete incontinence): 34% had a perfect continence, 58% suffered from mild to moderate symptoms, and 7% suffered from severe incontinence (> 14 score points). One patient from the latter group required elective-surgery (grade III toxicity). Fortyseven percent of the women, who were willing to talk about vaginal symptoms, stated moderate or severe dyspareunia or strictures. Apart from that no EORTC/RTOG grade 3 or higher adverse event occurred. Thirty-six percent of the patients stated to be considerably bothered by treatment effects. There was no significant difference in late symptoms according to treatment group, although patients in the IMRT/VMAT group received higher doses. Conclusions: In patients with anal cancer high precision radiation techniques allow the application of higher doses to the primary tumour and thus increase local control without increasing late symptoms. A longer follow-up and more patients under observation are needed to verify these results. PO-0718 Helical Tomotherapy in combined anal cancer treatment: a prospective trial with reduced overall treatment time S. Vagge1, A. Bacigalupo1, L. Belgioia1, D. Agnese1, R. Corvò2 1 IRCCS San Martino IST, Radiation oncology, Genova, Italy 2 IRCCS San Martino IST and University, Radiation oncology, Genova, Italy Purpose/Objective: Intensity Modulated Radiation Therapy (IMRT) allows the acute toxicity reduction in the concurrent chemo-radiotherapy (CTRT) treatment of the anal canal cancer (RTOG 0529). The overall treatment time(OTT) of the combined modality can affect the local control (Ben-Josef JCO 2010). We report preliminary results of a prospective trial with IMRT by Helical Tomotherapy (HT) delivered in a shortened OTT with the aim to reduce acute toxicity and potentially increase local control (LC). Materials and Methods: Between April 2009 and March 2013 twentyseven patients with anal canal cancer underwent to a combined CT-RT treatment with a RT schedule hypofractionate by a simultaneous integrated boost (SIB). The total dose was delivered on the basis of the T stage. The median dose prescribed and delivered to the pelvis was 45 Gy (41.4-45) while the primary tumor and positive nodes received 55 Gy(50.6-55) by a SIB over 25 (22-25) daily fractions. The standard chemotherapy regimen was mitomycin C (MMC) and 5-fluorouracil (5-FU) during the first and the last week of RT. Acute toxicity was registered following the common terminology criteria for adverse events (CTCAE v.3). The overall survival (OS),disease free survival (DFS) and colostomy free survival (CFS) were estimated by Kaplan Meier method. Results: The 67% of treated patients were in stage II and the 18% and15% were respectively in stage II and I (table I). The median OTT was 35 days(32-38). No RT interruptions due to acute toxicity have been reported. Planned concomitant chemotherapy was delivered to 23 (85%) patients, while 4 (15%) patients received capecitabine instead of standard CT. Gastrointestinal (GI),genitourinary (GU) and cutaneous
ESTRO 33, 2014 grade 2 acute toxicity were reported respectively in 5 (19%), 2 (7%) and 15 (56%) patients. Only a grade 3 of skin toxicity was registered in 5 (19%) of treated patients. After a median follow-up of 30 months (range 6-52) the estimated CFS, DFS and OS are 88%, 70%and 85% respectively.
Conclusions: Preliminary results suggest that IMRT-SIB by HT can be feasible with low incidence of acute toxicity, probably through shortened OTT. Good outcomes reported can encourage the technique. PO-0719 Multidisciplinary assessment in patients with anal canal carcinoma: simultaneous integrated boost with VMAT C. Iftode1, A. Tozzi1, T. Comito1, M. Federico2, E. Villa1, E. Clerici1, A. Gaudino1, G. Maggi1, F. Lobefalo1, M. Scorsetti1 1 Humanitas Clinical and Research Center, Radiotherapy and Radiosurgery, Rozzano (Milan), Italy 2 Università di Palermo, Radiotherapy, Palermo, Italy Purpose/Objective: To evaluate acute and late toxicity and clinical outcomes in patients with anal squamous cell carcinoma treated with volumetric modulated radiation therapy (VMAT) and concomitant chemotherapy. Materials and Methods: Patients with anal squamous cell carcinoma, age<75 years and good performance status (PS 0-1) underwent to concurrent chemo-radiotherapy. Multidisciplinary assessment was performed for all patients. Total body computed tomography (CT) scan, pelvic MRI with contrast enhancement, transanal endoscopic ultrasound with biopsy and colonoscopy were performed in each patient before treatment. All patients underwent CT simulation with oral and intravenous contrast enhancement. In six patients with positive lymph nodes was also performed PET-CT simulation. VMAT radiotherapy was delivered with a simultaneous integrated boost technique (SIB) . The prescription dose was 49.5Gy to the pelvic lymph nodes and 59.4 Gy to primary tumor and PET- positive nodes in 33 fractions with a dose per fraction of 1.5Gy and 1.8 Gy respectively. Cone beam CT imaging (CBCT) was performed before every treatment session to verify the exact position of the patient. 35 patients underwent to concomitant chemotherapy with 5-fluorouracil and mitomycin C (NIGRO) and 3 patients received 5 –fluorouracil and cisplatin. Acute and late toxicities were scored using the RTOG and CTCAE v. 4.0 respectively. Evaluation of tumour response was defined according to the Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1. Results: From January 2010 to September 2013, 38 patients were treated. In 91% of cases the treatment was completed without interruption. In 9% of patients occurred acute gastrointestinal toxicity G3 , while 17 % had acute dermal toxicity G3 in the perianal area. No patient experienced late toxicity grade 3. With a median follow-up of 25 months, the local control rate at 1 year was 100 %, with 82% of patients with complete response (CR ) of disease. In 18% of cases we obtained a partial response (PR). Conclusions: Treatment with volumetric modulated radiation therapy (VMAT) delivered with simultaneous integrated boost (SIB) and concomitant chemotherapy was well tolerated, with an acceptable rate of acute and late toxicity and with excellent local control of disease. PO-0720 Association between life prognosis and pretreatment ICG 15 for the patients with HCC treated by proton beam therapy M. Mizumoto1, Y. Oshiro1, T. Okumura1, N. Fukumitsu1, H. Ishikawa1, K. Ohnishi1, H. Numajiri1, T. Aihara1, K. Tsuboi1, H. Sakurai1 1 University of Tsukuba, Radiation Oncology, Tsukuba, Japan Purpose/Objective: Child-Pugh score is known as an important factor for results of radiotherapy for hepatocelular carcinoma (HCC). On the other hand, retention rate of indocyanine green 15 minutes (ICG 15) after
UMC Utrecht, Oncologic Surgery, Utrecht, The Netherlands Julius Center, Clinical Epidemiology, Utrecht, The Netherlands
5
Purpose/Objective: Randomized controlled trials (RCTs) often experience difficulties in recruitment, external validity, follow-up, and comparability. These shortcomings become progressively important when the clinic can hardly keep up with newly available innovative treatments. We introduced the ‘cohort multiple Randomized Controlled Trial’ (cmRCT) (1), which was designed to efficiently and simultaneously evaluate new interventions, in our center. Materials and Methods: The basis of our cmRCT-design consists of a prospective observational cohort (‘ProspectIve data CollectioN Initiative on Colorectal cancer’ (PICNIC) project) in which patients optionally give separate informed consents for collection of their 1) clinical, 2) patientreported, and 3) biobank data (tumor tissue and blood samples) for (comparative) research. In a separate informed consent, they are asked to consent to 4) being randomly offered experimental interventions in the future. In practice: Rectal cancer patients that meet inclusion criteria for the experimental radiation Boost intervention are identified from all who have previously consented to experimental treatment offers. From this sub-cohort randomly selected patients are offered this Boost, which they may than accept or refuse (if standard treatment is preferred). All other patients that were not randomly selected will receive standard treatment, serving as the control-group, and will not be notified about the experimental intervention. Nevertheless, they are aware of, and have already given informed consent for their clinical and self reported data to be used for comparative research. Data is analyzed by ‘intentionto-treat’ principle, and additionally by ‘per-protocol’ or ‘complier average causal effect’ methods. Results: In the past 9 months 91 of 117 (78%) rectal cancer patients at the Radiotherapy department consented to participation in the PICNIC project (cohort). A subset of 97 patients (88%) has given separate informed consent to offer them experimental treatments. Of all eligible ‘boost-study’ subjects ..%* accepted and underwent the offered boost treatment. *nt: Patient recruitment is ongoing and updated number will be presented Conclusions: Cohort participation rate is higher than observed in conventional RCTs. A greater proportion of patients accepts ‘cohortbased random selection’ compared to ‘conventional randomization’. Efficient recruitment may contribute to improved statistical power and reduced trial-duration. This is of major interest in a time when new treatment modalities and innovations demand efficient (and rapid)evaluation. 1. Relton C. et al. Rethinking pragmatic randomised controlled trials: introducing the 'cohort multiple randomised controlled trial' design., BMJ. 2010;340:c1066. PO-0715 Post-neoadjuvant presacral radiological abnormalities in rectal cancer: Long-term risk factors analysis M. Muñoz1, F.A. Calvo1, J. Serrano1, C. Calles1, J. Laureiro1, L. Martín1, M. Gómez-Espí1, E. Del Valle2 1 Hospital Gregorio Marañón, Oncología Radioterápica, Madrid, Spain 2 Hospital Gregorio Marañón, Cirugía General, Madrid, Spain Purpose/Objective: Radiological abnormalities in the presacral area (RAPA) after neoadjuvant treatment for locally advanced rectal cancer (LARC) are complex to interpret in terms of clinical and pronostic implications. Long-term radiological changes in the posterior hemipelvis are analyzed in the context of potential risk factors for development. Computerized tomography (CT) observations are categorized to discriminate malignant versus non-malignant changes. Materials and Methods: From 04/95 to 12/10, 397 patients with LARC [≥ cT3 (93%) and/or cN + (69%)] were treated with preoperative external pelvic irradiation (81% ≥ 4500cGy) concurrent to fluoropirimidine based chemotherapy,radical surgery (sphincter preserving 68%) and presacral electron irradiation boost (IeORT) (83%). Elective adjuvant chemotherapy was considered. IeORT common characteristic were: single dose 12.5Gy (27%), electron energies 12MeV (33%), applicator diameter 5/6 cm (65%), beveled end 45º (96%). Results: With a median follow-up of 63 months, RAPA was documented in 48% of patients. Evolutive clinical and radiological subtypes were classified as presacral recurrence (4%), non-malignant mass (23%) or fibrotic linear scarring (20%). Overall survival at 5 and 10 years were 8%/0%,68%/46% and 86%/77%, respectively. Features related to the development of RAPA were: abdominoperineal resection and anterior
S27 ultralow resection (p 0,010); postoperative complications involving infection, wound dehiscence and bleeding episodes (p=0,00); operation room time (p 0,00); and ypN+ specimens (p 0,016). Non-presacral intrapelvic recurrences included 12 anastomotic (3%), 2 vaginal (0.5%), 1 urethral (0.3%) and 3 lateral pelvic sided nodes (0.8%). Conclusions: The development of post-neoadjuvant RAPA is a frequent and heterogeneous follow-up event. Risk factors identified are associated to pelvic surgical stress features and radioresistant cancer. The evolutive trend appears to be related to imaging patterns and oncological nature. In clinical practice post-neoadjuvant RAPA is rarely rectal cancer recurrence (4%). PO-0716 Image guided SBRT for treatment of liver malignancies: review of single institution 4-year experience O. Utehina1, I. Nemiro2, G. Boka1, D. Purina1, S. Maksimova1, J. Frolova1, S. Popov1, V. Boka3 1 Riga East University Hospital, Clinic of Therapeutic Radiology and Medical Physics, Riga, Latvia 2 University of Latvia, Faculty of Medicine, Riga, Latvia 3 Riga East University Hospital, Clinic of Surgery, Riga, Latvia Purpose/Objective: The purpose of this study was to evaluate intermediate term results of liver Stereotactic Body Radiotherapy (SBRT) from point of view of clinical safety and clinical effectiveness. Materials and Methods: 40 patients with 54 malignant lesions in liver treated with SBRT between 2009 and 2013 were included in analysis: 10 patients had primary liver tumors (6-hepatocellular carcinoma, 4 Klatskin tumor) and 30 had metastasis (18 from colorectal cancer and 12 from other tumor sites). Free breathing Four-dimensional Computed Tomography (4DCT) based planning was performed for all patients. No external fixation devices were used except a vacuum bag. Gross Tumor Volume (GTV), Clinical Target Volume (CTV), and Internal Target Volume (ITV) were contoured on the basis of MRI images co-registered with Maximum Intensity Projection (MIP) CT. Dose delivery was performed in consecutive days using Image Guided Volumetric Modulated Arc Therapy (IGVMAT). Prescribed dose per fraction varied from 7 to 18 Gy. Minimum PTV dose was in the range of 30 – 48 Gy. Follow-up MRI imaging was performed for all patients. This allowed to access status of tumor after treatment as well as to evaluate precision of dose delivery by imaging of typical parenchymal tissue changes arising in high dose volume after SBRT. Influence of various treatment and tumor parameters on overall survival and local relapse free survival was studied. Results: Follow-up time was in range of 5 to 49 months with median follow-up time of 13 months. Initial follow-up IMR imaging has shown that in all cases initial lesions were confined within volume of parenchymal changes. No one of the patients had any acute or late adverse effects after treatment. For four patients re-treatment by SBRT was performed due to local or other recurrence inside liver. Median overall survival was 29 months. 24-month overall survival was 53%. Distant relapse outside of the liver and initial number of liver lesions affected overall survival. Median overall survival for patients with distant relapse and without was 17 months and 36 months, respectively (p = 0.045). For patients with multiple lesions median overall survival was 13 months comparing to 29 months for patients with solitary tumor (p = 0.041). Median local recurrence free survival was 19 months. 24month local recurrence free survival was 49%. Frequency of local recurrence was affected by level of prescribed dose. 24-month local recurrence free survival was 40% for patients, which received doses ≤36 Gy and 59% for patients, which received doses above 36 Gy (p= 0.015). Conclusions: According to the intermediate term clinical experience analyzed in this study, SBRT for liver cancer is effective and safe. IGVMAT SBRT is easy to use, provides a high targeting precision, is well tolerated by patients and can be applied for retreatment. Data analysis shows that further dose escalation is needed for the better local tumor control. This possibility has to be evaluated by further studies of dose – effect relationships. Nevertheless, the study results are very promising and clearly demonstrate superiority of SBRT in treatment of liver tumors. PO-0717 Radiotherapy of anal cancer: Is IMRT and VMAT a step forward? G. Gruber1, C. Track1, C. Venhoda1, J. Hammer1, B. SpindelbalkerRenner1, E. Putz2, K.J. Spiegl1, H. Geinitz1 1 Krankenhaus Barmherzige Schwestern, Radiation Oncology, Linz, Austria 2 Krankenhaus Barmherzige Schwestern, Radiation Oncology Physics Section, Linz, Austria
S28 Purpose/Objective: In the treatment of anal cancer, intensitymodulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT, RapidArc©) were implemented at our department in 2006 and 2010, respectively. For three years we apply these techniques now to all our patients with anal cancer of all stages. To report the effect of these implementations on efficacy and toxicity we analysed all patients with anal cancer treated at our institution during the last decade. Materials and Methods: Patients who reached a complete remission 6 months after treatment were included in the evaluation (n=89, female: 65, male: 24). Fifty seven were treated with conventional techniques (mostly 3D-conformal), 9 with IMRT and 23 with VMAT. For conventional techniques the median dose was 56 Gy to the primary tumour (PT), 50 Gy to the pelvic nodes (PN) and 40 Gy to the inguinal nodes (IN). For IMRT/VMAT the respective figures were 60 Gy (PT), 50 Gy (PN) and 36 Gy (IN). Concurrent chemotherapy (5-FU with or without Mitomycin C) was administered to 83% (79% conventional and 91% IMRT/VMAT). Follow-up examinations, including MRI of the pelvis, were performed at regular intervals. A questionnaire regarding late radiation morbidity on pelvic organs as well as symptom-bother was answered by 45 patients after a median follow-up of 4 years. Results: For the whole cohort, the overall survival at 5 years was 85% and the disease specific survival 92% without differences according to treatment technique. The rates for local control, loco-regional control and disease-free survival were 88%, 82% and 75% with a trend to better rates in the IMRT/VMAT group. Mild to moderate late symptoms regarding defecation and micturition were reported by 63% and 67% of the patients, respectively. Anal incontinence was graded according to the Jorge-Wexner-Score (0 perfect continence; 20 - complete incontinence): 34% had a perfect continence, 58% suffered from mild to moderate symptoms, and 7% suffered from severe incontinence (> 14 score points). One patient from the latter group required elective-surgery (grade III toxicity). Fortyseven percent of the women, who were willing to talk about vaginal symptoms, stated moderate or severe dyspareunia or strictures. Apart from that no EORTC/RTOG grade 3 or higher adverse event occurred. Thirty-six percent of the patients stated to be considerably bothered by treatment effects. There was no significant difference in late symptoms according to treatment group, although patients in the IMRT/VMAT group received higher doses. Conclusions: In patients with anal cancer high precision radiation techniques allow the application of higher doses to the primary tumour and thus increase local control without increasing late symptoms. A longer follow-up and more patients under observation are needed to verify these results. PO-0718 Helical Tomotherapy in combined anal cancer treatment: a prospective trial with reduced overall treatment time S. Vagge1, A. Bacigalupo1, L. Belgioia1, D. Agnese1, R. Corvò2 1 IRCCS San Martino IST, Radiation oncology, Genova, Italy 2 IRCCS San Martino IST and University, Radiation oncology, Genova, Italy Purpose/Objective: Intensity Modulated Radiation Therapy (IMRT) allows the acute toxicity reduction in the concurrent chemo-radiotherapy (CTRT) treatment of the anal canal cancer (RTOG 0529). The overall treatment time(OTT) of the combined modality can affect the local control (Ben-Josef JCO 2010). We report preliminary results of a prospective trial with IMRT by Helical Tomotherapy (HT) delivered in a shortened OTT with the aim to reduce acute toxicity and potentially increase local control (LC). Materials and Methods: Between April 2009 and March 2013 twentyseven patients with anal canal cancer underwent to a combined CT-RT treatment with a RT schedule hypofractionate by a simultaneous integrated boost (SIB). The total dose was delivered on the basis of the T stage. The median dose prescribed and delivered to the pelvis was 45 Gy (41.4-45) while the primary tumor and positive nodes received 55 Gy(50.6-55) by a SIB over 25 (22-25) daily fractions. The standard chemotherapy regimen was mitomycin C (MMC) and 5-fluorouracil (5-FU) during the first and the last week of RT. Acute toxicity was registered following the common terminology criteria for adverse events (CTCAE v.3). The overall survival (OS),disease free survival (DFS) and colostomy free survival (CFS) were estimated by Kaplan Meier method. Results: The 67% of treated patients were in stage II and the 18% and15% were respectively in stage II and I (table I). The median OTT was 35 days(32-38). No RT interruptions due to acute toxicity have been reported. Planned concomitant chemotherapy was delivered to 23 (85%) patients, while 4 (15%) patients received capecitabine instead of standard CT. Gastrointestinal (GI),genitourinary (GU) and cutaneous
ESTRO 33, 2014 grade 2 acute toxicity were reported respectively in 5 (19%), 2 (7%) and 15 (56%) patients. Only a grade 3 of skin toxicity was registered in 5 (19%) of treated patients. After a median follow-up of 30 months (range 6-52) the estimated CFS, DFS and OS are 88%, 70%and 85% respectively.
Conclusions: Preliminary results suggest that IMRT-SIB by HT can be feasible with low incidence of acute toxicity, probably through shortened OTT. Good outcomes reported can encourage the technique. PO-0719 Multidisciplinary assessment in patients with anal canal carcinoma: simultaneous integrated boost with VMAT C. Iftode1, A. Tozzi1, T. Comito1, M. Federico2, E. Villa1, E. Clerici1, A. Gaudino1, G. Maggi1, F. Lobefalo1, M. Scorsetti1 1 Humanitas Clinical and Research Center, Radiotherapy and Radiosurgery, Rozzano (Milan), Italy 2 Università di Palermo, Radiotherapy, Palermo, Italy Purpose/Objective: To evaluate acute and late toxicity and clinical outcomes in patients with anal squamous cell carcinoma treated with volumetric modulated radiation therapy (VMAT) and concomitant chemotherapy. Materials and Methods: Patients with anal squamous cell carcinoma, age<75 years and good performance status (PS 0-1) underwent to concurrent chemo-radiotherapy. Multidisciplinary assessment was performed for all patients. Total body computed tomography (CT) scan, pelvic MRI with contrast enhancement, transanal endoscopic ultrasound with biopsy and colonoscopy were performed in each patient before treatment. All patients underwent CT simulation with oral and intravenous contrast enhancement. In six patients with positive lymph nodes was also performed PET-CT simulation. VMAT radiotherapy was delivered with a simultaneous integrated boost technique (SIB) . The prescription dose was 49.5Gy to the pelvic lymph nodes and 59.4 Gy to primary tumor and PET- positive nodes in 33 fractions with a dose per fraction of 1.5Gy and 1.8 Gy respectively. Cone beam CT imaging (CBCT) was performed before every treatment session to verify the exact position of the patient. 35 patients underwent to concomitant chemotherapy with 5-fluorouracil and mitomycin C (NIGRO) and 3 patients received 5 –fluorouracil and cisplatin. Acute and late toxicities were scored using the RTOG and CTCAE v. 4.0 respectively. Evaluation of tumour response was defined according to the Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1. Results: From January 2010 to September 2013, 38 patients were treated. In 91% of cases the treatment was completed without interruption. In 9% of patients occurred acute gastrointestinal toxicity G3 , while 17 % had acute dermal toxicity G3 in the perianal area. No patient experienced late toxicity grade 3. With a median follow-up of 25 months, the local control rate at 1 year was 100 %, with 82% of patients with complete response (CR ) of disease. In 18% of cases we obtained a partial response (PR). Conclusions: Treatment with volumetric modulated radiation therapy (VMAT) delivered with simultaneous integrated boost (SIB) and concomitant chemotherapy was well tolerated, with an acceptable rate of acute and late toxicity and with excellent local control of disease. PO-0720 Association between life prognosis and pretreatment ICG 15 for the patients with HCC treated by proton beam therapy M. Mizumoto1, Y. Oshiro1, T. Okumura1, N. Fukumitsu1, H. Ishikawa1, K. Ohnishi1, H. Numajiri1, T. Aihara1, K. Tsuboi1, H. Sakurai1 1 University of Tsukuba, Radiation Oncology, Tsukuba, Japan Purpose/Objective: Child-Pugh score is known as an important factor for results of radiotherapy for hepatocelular carcinoma (HCC). On the other hand, retention rate of indocyanine green 15 minutes (ICG 15) after